Coronavirus disease 2019 (COVID-19)diagnosis is based on molecular detection of SARS-CoV-2 in respiratory samples such as nasal swab (NS). However, the evidence that NS in patients with pneumonia were sometimes negative raise the attention to collect other clinical specimens. SARS-CoV-2 was shown in 10.3%rectal swabs (RS), 7.7% plasma,1% urine, 0% feces from 143NS positive patients. Potential infection by fluids different from respiratory secretion is possible but unlikely.
Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by Aspergillus induced hypersensitivity that occurs in immunocompetent but susceptible patients with asthma and/or cystic fibrosis (CF). In children, ABPA remains mostly undiagnosed, resulting in one of the most common causes of poorly controlled asthma and highly significant morbidity in children with CF. Currently, no specific diagnostic criteria of ABPA for children are available. Corticosteroids and itraconazole are the mainstays of therapy, althoughthere is a lack of randomized clinical trials regarding their usefulness for ABPA in children. Several monoclonal antibodies, such asomalizumab and mepolizumab, may be potential therapies for refractory ABPA in pediatric patients; however, further data are required to clarify the optimal dose and duration of therapy as a routine treatment approach.
Epidemiologic studies performed in the Melbourne Sexual Health Center over several years have explored and emphasized the role of sexual transmission in the pathogenesis of sporadic bacterial vaginosis (BV) as well as recurrent BV (Fethers KA., et al. Infect. Dis. 2008; 47: 1426-1435). Some of the most definitive studies documenting details of heterosexual sexual transmission followed. There can be little doubt as to the causal role of sexual transmission in BV particularly with regard to the initial episode (Cherpes, TL., et al. Sex. Transm. Dis 2008; 35: 78-83). The present study adds solid molecular data to their previous epidemiologic data that recurrent BV is more likely to occur in a heterosexual woman with a single regular male partner (Ratten L., et al BJOG 2020 xxxx): Moreover, the risk is mitigated by use of an oral contraceptive and barrier contraceptives. Specifically, Ratten et al conclude that sex is associated with persistence of non-optimal, BV-associated vaginal dysbiosis following appropriate antimicrobial treatment for BV in a cohort followed prospectively, likely the result of sexual transmission from a regular partner. The key term used in the title of the study is persistence, which implies that the non-optimal vaginal microbiota fails to resolve, as opposed to future reintroduction from the same guilty partner. Persistence in this context, unfortunately, also indirectly suggests that inadequate antimicrobial treatment is currently prescribed to women, perhaps sufficient to relieve symptoms and meet diagnostic criteria of satisfactory response, but insufficient to eradicate BV pathogens. The author emphasizes needed improvement in the, so far, futile male partner therapy to prevent female reinfection, a goal that has repeatedly eluded experts to date.The unanswered question facing patients and clinicians alike is the role of sexual reinfection as opposed to vaginal relapse in the causation and likelihood of BV recurrence. The tone of the article would indicate that reinfection is the more likely causal mechanism of BV recurrence, by emphasizing “persistence” and outweighing the role of unexplained relapse. In dealing with a symptomatic patient suffering from an episode of recurrent BV, it is currently not possible to differentiate relapse from reinfection unless the patient declares herself to be celibate, ergo relapse is the cause of recurrence. The clinical picture is identical as are Amsel or Nugent criteria. Unfortunately, molecular microbiome studies have not revealed significant differences between sequential episodes regardless of causation. We lack a “unique fingerprint” to differentiate cause or nature of the recurrent episode. Even with reinfection, sexual or otherwise, details of pathogenesis are still lacking. We know too that coitus can elicit symptoms of BV (post coital malodor) even with use of a condom. The role of receptive oral-vulvovaginal sex is also undetermined, as is the role of penile – anorectal penetration although the latter was found to be minimal in the latest study by Ratten L., et al. (BJOG 2020 xxxx): Moreover, not all longitudinal studies have revealed that heterosexual sex is a major factor in recurrence (Sobel J.D., et al. Infect. Drug Resist. 2019: 12; 2297-2307).The role of sex and reinfection in causation of RBV will depend significantly upon the population studied, including biologic and behavioral differences. Determination of causation of BV recurrence in different patient populations should be personalized and acknowledged as we admit our current limitations. Will more effective male treatment help reduce BV recurrence? Hopefully but still unknown. Determining all the causes of vaginal microbiota persistence, including the role of biofilm, remains a challenge.No disclosures: A completed disclosure of interest form is available to view online as supporting information.
This program director survey attempts to determine how coronavirus 2019 (COVID-19) pandemic is impacting current training in cardiothoracic surgery. A transition to virtual didactic sessions may prove beneficial with increasing attendance. On the other hand, decreasing live simulation and case volumes may jeopardize achieving competency in surgical skills.
We present a complication following deployment of the MANTA VCD device following a TAVR procedure which resulted in occlusion of the common femoral artery. This was addressed by ballooning the site from the contralateral side which re-established flow. We believe this is the first report to address this kind of complication and may prove useful as more of the MANTA devices are being used in multiple procedures.
Polyandry, when females mate with more than one male, is theorised to play an important role in successful colonisation of new habitats. In addition to possible benefits from sexual selection, even mild polyandry could facilitate colonisation by protecting against inbreeding and reducing the costs of mating with incompatible or infertile males. Here, we measure the importance of mild polyandry for population viability and reproductive fitness following experimental founder events into a higher temperature regime. Using colonisation experiments with the model beetle Tribolium castaneum, in which females can produce offspring for up to 140 days following a single mating, we founded more than 100 replicate populations using single females that had been given the opportunity to mate with either one or two males, and then tracked their subsequent population dynamics. Following population viability and fitness across ten generations, we found that extinction rates were significantly lower in populations founded by females given polyandrous opportunities to mate with two males (9%) compared to populations founded by monogamous females (34%). In addition, populations founded by females that had been provided with opportunities to store sperm from two different males showed double the median productivity following colonisation compared to monogamous-founded populations. Notably, we identified short-term and longer-term benefits to post-colonisation populations from double-mating, with results suggesting that polyandry acts to both protect against mating with incompatible males through the founder event, and reduce inbreeding depression as the colonisation proceeds for ten generations. Our results therefore show that even mild polyandry provides both reproductive and genetic benefits for colonising populations.
Ant Forest, a mobile app by the monolithic Alibaba Group, is greening individuals' daily activities and transforming human capacity to reverse global environmental degradation. Over 500 million e-trees being cultivated every day in China using Ant Forest. Over 122 million trees planted over more than 112,000 ha of degraded land areas. This is a showcase of how innovation via internet technology combined with digital finance is contributing to solving environmental issues, also the potential to match an individual's daily footprint to their digital footprint and converting this to an ecological footprint.
Right superior vena cava draining in the left atrium is a rare anomaly, commonly associated with other cardiac defects. Herein we present the case of a 9 year old patient, asymptomatic but with right heart dilation with sinus venous defect, bilateral superior vena cavas with the right draining into the left atrium.
Drug hypersensitivity reactions (DHRs) represent a global threat to healthcare systems due to their incidence, with a significant increase over last years1. DHR figures are overestimated in the general population since less than 40% of cases initially labelled as allergic can be confirmed as such when evaluated in an allergy unit2. Achieving an accurate diagnosis is complex and time consuming; besides, tests must be tailored to specific clinical manifestations and underlying mechanisms and will depend on the culprit drugs. Diagnosis often requires performing drug provocation tests (DPTs), which are especially problematic for severe reactions, making management of these patients challenging and expensive for the health care system.Clinically, DHRs are classified into immediate and non-immediate, based on the time interval between drug exposure and onset of the symptoms3. The most severe immediate reaction is anaphylaxis. This issue of the journal has been dedicated o drug hypersensitivity, which is becoming a major public health issue during the last decade, especially with the introduction of biologicals to medicine. Bilo et al. 4 evaluated the anaphylaxis mortality rate in Italy from 2004 to 2016 and found an average mortality rate for definite anaphylaxis (ICD-10 code) of 0.51 per million population per year, mostly due to the use of medications (73.7%), although in 98% of the cases culprit drugs were not identified. Regarding non-immediate reactions, one of the most challenging diagnoses is drug reaction with eosinophilia and systemic symptoms (DRESS), which is sometimes difficult, at an early stage, due to overlapping clinical symptoms with maculopapular exanthema (MPE). Pedruzzi et al. 5 identified 7 microRNAs (miRNAs) that correctly classified DRESS or MPE patients and were associated with keratinocyte differentiation/skin inflammation, type I IFN pathway viral replication, ATP-binding cassette transporters, and T lymphocyte polarisation, being all of them potential biomarkers. Non-immunologically mediated adverse reactions, such as attention-deficit/hyperactivity disorder (ADHD) are reported by Fuhrmannet al. 6 in association with systemic H1-antihistamines administration in school-age children, especially the 1st generation agents.The mechanism underlying DHR and the reason why patients treated with the same drug develop a tolerance response or an immediate or non-immediate DHR is not completely understood (Figure 1). Therefore, the prediction of who may experience a DHR, and if so, in what form, remains clinically obscure for most drugs. Goh SJR et al. 7 elegantly analyse this complexity, using non-immediate reactions to penicillins as a model. They focus on the understanding of the role of nature of the lesional T cells, the characterisation of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen-processing and presentation pathway to stimulate these deleterious responses.Regarding specific drugs involved in allergy, betalactam antibiotics (BL) are the most frequent culprit, being many reactions mediated by IgE. This type of reaction varies among patients, with some reacting only to one BL and others to several of them; it tends to change over time and differs between European countries, depending on BL consumption. Nowadays, amoxicillin (AX), alone or in combination with the β-lactamase inhibitor clavulanic acid (CLV), is the most often prescribed BL worldwide (Figure 2) and the most common elicitor of reactions in both children and adults. It is unclear why patients after the administration of AX-CLV develop selective hypersensitivity to AX, while tolerating CLV and vice-versa. Ariza et al. 8 generated drug-specific T-cell clones from AX- or CLV-selective immediate hypersensitivity patients and found that both AX- and CLV-specific clones were generated irrespective of whether AX or CLV was the culprit, although a higher secretion of Th2 cytokines (IL-13 and IL-5) was detected when clones were activated with the culprit BL compared with clones stimulated with the tolerated BL, in which higher secretion of Th1 cytokines (IFN-γ) was observed. Regarding selective non-immediate reactions to CLV, Copaescu A et al. 9 report on a cohort of patients with a history of non-immediate reaction to CLV, who demonstrated a delayed intradermal skin test response to CLV, 17% were allergic to both CLV and ampicillin, and 83% were selective reactors with good tolerance to AX. IFN-γ release enzyme-linked immunospot (ELISpot) was performed giving a sensitivity of 33%. Other drugs such as sulphonamides, either antibiotic or non-antibiotics are important triggers of non-immediate DHRs. Vilchez-Sanchez et al. 10 showed that lymphocyte transformation tests (LTT) can help avoid the performance of DPT with a sensitivity of 75%, a specificity of 100%, and negative and positive predictive values of 72.7% and 100%, respectively.There has been a great expansion in the use of biological agents (mainly monoclonal antibodies (mAbs)), and they have greatly improved the treatment landscape of hemato-oncologic, autoimmune, inflammatory and rheumatologic diseases. In parallel, the incidence rate of reported DHRs associated with these products has increased considerably within the last years, ranging from mild to life-threatening. Yang BC et al. 11 recommend risk stratification as the first step for managing patients with DHRs to these drugs. In cases with negative skin test and mild reactions, DPT is an option, and in moderate or severe reactions, desensitisation becomes the preferred approach. In cases with positive skin test, desensitisation is the recommended course of action, especially when there is no alternative medication. Desensitisation is also widely used in the management of immediate hypersensitivity reactions to chemotherapy agents, such as platinums. There is suspicion about the presence of a longer memory of tolerance in subsequent desensitisation protocols partially resembling the regulatory tolerance mechanisms induced by allergen immunotherapy. Tüzer et al. 12 demonstrate the possible role of IL-10 in desensitisation with platinums, as they found a dynamic change in serum IL-10 levels observed as an increase during desensitisation and a decrease in between the protocols.Finally, a wide spectrum of drugs has been considered for treatment of coronavirus disease 2019 (COVID-19) and all of them can potentially induce DHRs. Gelincik A et al .13 reviewed DHRs in COVID-19 times to these drugs, with knowledge mainly coming from previous clinical experience in patients not infected with COVID-19. As in other viral infections, skin symptoms, including exanthemas, may appear during the evolution of the disease, leading to differential diagnosis with DHRs. Whether COVID-19 can aggravate T–cell mediated DHRs reactions as some viruses is at present unknown.We can conclude that new drugs are continuously introduced into the markets and confirmed as inducers of hypersensitivity reactions. We still do not completely understand the mechanisms underlying many of these reactions and further studies for improving diagnostic and management are needed even in classic and well-studied drugs as BLs.Abbreviations: AX: Amoxicillin; CLV: Clavulanic acid; COVID-19: Coronavirus disease 2019; DHR: Drug hypersensitivity reactions; DPT: Drug provocation tests; DRESS: Drug reaction with eosinophilia and systemic symptoms; ELISpot: enzyme-linked immunospot; LTT: Lymphocyte transformation tests; MPE: Maculopapular exanthema.
Providing complex therapies such as ECMO during outbreaks of infectious diseases has singular challenges. The impact of the SARS-CoV-2 pandemic has implied a mentality change by force of circumstances, and cardiac surgery has not been stranger to this trend. The need to treat critically ill patients with an unknown evolution has compelled cardiovascular surgeons to decide whether or not to implant an ECMO system, despite the limited scientific evidence available in the context of COVID-19. To add some confusion, doubts were raised about its potential deleterious outcome in COVID-19 patients, due to its effect on lymphocyte counts and interleukin-6 concentrations. The care of the critically ill patient in a moment of national emergency in Spain took precedence over those possible formal doubts. The Spanish perspective on Ventricular Assist Devices during and after the COVID-19 pandemic, focused on ECMO as a particular case of mechanical circulatory support, is presented. We address both the challenges posed by the pandemic and the organizational model established in Spain; changes in ECMO therapy and some lessons learned for the next outbreaks are also described. It is not about reinventing the wheel in each country; it is enough to learn from experience and take advantage of the knowledge generated by those who have already gone through similar situations in our environment.
Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance, lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity.
Endometriosis is a common health condition affecting women of reproductive age who often present with chronic pelvic pain and/or infertility. There is wide variation in the estimates of endometriosis prevalence. Accurate reporting of the disease prevalence is hampered by multiple factors including long delay in diagnosis due to natural fluctuation in symptoms severity, lack of a reliable non-surgical diagnostic tool, polymorphic appearance of endometriosis lesions at laparoscopy, inability to achieve histological confirmation is all suspected cases and tendency for disease recurrence. Therefore, a longitudinal, rather than cross-sectional, cohort study design spanning an extended follow-up period is better suited to assess endometriosis prevalence. In this issue of BJOG, Rowlands and colleagues (2020) linked longitudinal survey data to three administrative health databases to identify the prevalence of endometriosis among 13,508 young Australian women followed up for nearly 20 years. The study reported a 6% cumulative prevalence of clinically-confirmed endometriosis and an additional 5.4% of clinically-suspected endometriosis. If these figures reflect the true prevalence of endometriosis, then one in nine women will be diagnosed with endometriosis at some point during their reproductive years up to the age of 44 with a peak at 30-34 years, thus underscoring the significant impact of the disease on the well-being and quality of life in young women and the enormous burden on healthcare resources needed to diagnose and treat endometriosis and its sequelae.The data presented in the study of Rowlands and colleagues (BJOG 2020) included patients who could have been diagnosed with adenomyosis but their condition was coded as endometriosis. This is unlikely to have significantly over-estimated the prevalence of endometriosis as recent evidence suggests adenomyosis prevalence to be only 1% with a considerable proportion of those patients having co-existing endometriosis (Yu et al, Am J Obstet Gynecol 2020; 223: 94.e1-10). The same can not be said about the 5.4% of clinically-suspected endometriosis cases. Symptoms review, clinical examination and various imaging modalities, including ultrasound scanning and magnetic resonance imaging, represent the cornerstone of non-invasive diagnosis of endometriosis. Current evidence suggests that the predictive accuracy of those non-invasive methods in the diagnosis of endometriosis compared to laparoscopy and histological confirmation is modest (Nisenblat et al, Cochrane Database Syst Rev, 2016 (2): CD009591) and depends on the combination of diagnostic tools used as well as the site and extent of the endometriosis lesions (Reid et al, Eur J Obstet Gynecol Reprod Biol 2019; 234: 171-178). These data are not provided in the study of Rowlands and colleagues. It is therefore difficult to accurately estimate the prevalence of endometriosis whether it’s the 6% clinically-confirmed rate or the full 11.4% confirmed and suspected rate. The truth probably lies somewhere in the middle! Future epidemiological studies should endeavour to elucidate on the distinction between the different methods used in the diagnosis of endometriosis with reference to the predictive accuracy of each diagnostic modality to help advance our understanding of the incidence and risk factors associated with this debilitating gynaecological condition.Mr. Tarek A El-ToukhyAssisted Conception Unit, Guys and St. Thomas Hospital NHS Trust11th Floor, Tower Wing,Guys Hospital,St. Thomas Street email@example.com
Our article reported risk factors for ICD lead failure at our medical center, and we found an elevated risk of ICD lead failure in multiple lead ICD systems implanted via cephalic venous access.(1) Our analysis was prompted by recent literature related to durability of the Linox ICD lead (Biotronik, Inc., Berlin, Germany), and we found similar, elevated risk of ICD lead failure implanted in multiple lead systems via cephalic access in Linox and non-Linox ICD leads. Given the small number of total lead failures in the overall cohort (6 of 660), and the retrospective, single-center nature of our analysis, we reviewed prior Linox ICD lead durability manuscripts for evidence of increased risk of failure in multiple lead ICD systems implanted via cephalic venous access. While no prior manuscript evaluated this specific risk, we did find a trend towards increased risk of lead failure in cohorts with greater proportions of multiple lead systems, and greater proportions of systems implanted via cephalic access, however these variables were included in the analysis in a minority of prior studies.Dr. Maas and colleagues express surprise at the high failure rate when implanting multiple leads in our cohort. We would clarify that we reported ICD lead failure in 4 of the 304 patients in our cohort with multiple ICD leads, and that the frequency of lead failure in multiple lead ICD systems was not statistically significantly different compared to that of single lead ICD systems. In contrast, and surprisingly to us, 3 of 30 patients with multiple lead ICD systems implanted via cephalic access experienced ICD lead failure, and the frequency of ICD lead failure was significantly greater in this group compared to the remaining cohort in Kaplan-Meier survival analyses.Maas and colleagues question the reason for utilization of cephalic access in 18% of patients, hypothesize that suboptimal implantation technique may be responsible for the elevated lead failure rate, and request clarification of lead failure mechanism. We did not systematically collect rationale for venous access technique, and venous access techniques was at the discretion of the implanting physician. Of the 6 lead failures, 3 were related to lead noise, and 3 were related to rising pacing thresholds. Of the three lead failures amongst patients with multiple lead systems implanted via cephalic venous access, 2 were related to lead noise, and 1 was related to a rising pacing threshold. We believe that the lead noise may be related to insulation breach that may be predisposed by lead-lead interactions in the region of the cephalic vein. ICD leads were returned to the manufacturer on an ad hoc basis, and no specific feedback was received from manufacturers related to leads included in our analysis. All implanting physicians were experienced operators, and there were no significant differences in frequency of ICD lead failure by operator. We agree that implantation technique may play an important role in lead failure risk, and our analysis should prompt extra caution when implanting multiple leads via cephalic venous access.Citing the above limitations of our analysis, Dr Maas and colleagues state that it is “too early to abandon cephalic vein access, even for multiple lead systems.” They also review recent literature reporting favorable acute outcomes of ultrasound guided axillary venous access. We agree that our analysis paired with our literature review is best considered hypothesis generating, and we hope that our analysis encourages future studies to consider our findings when selecting variables of interest in ICD lead durability studies. We share Dr. Maas and colleagues’ favorable view of data supporting axillary venous access, particularly in combination with ultrasound guidance. As a result, given the available evidence of acceptable alternative techniques, our practice is to favor axillary venous access during implantation of multiple lead ICD systems, but we would not hesitate to implant via cephalic venous access in the appropriate clinical scenario.References1. Barbhaiya CR, Niazi O, Bostrom J et al. Early ICD lead failure in defibrillator systems with multiple leads via cephalic access. Journal of cardiovascular electrophysiology 2020;31:1462-1469.
The activity of influenza A at the end of 2019 was higher than previous two years in children younger than 6 years old in Wuhan, China. The 2019-20 seasonal influenza winter outbreak preceded the COVID-19 outbreak, with a higher and earlier peak than that of the 2017-18 and 2018-19 seasons. We speculate this could be due to the earlier CNY holiday season in 2019-20 than in previous two years. We compared these results with those of two previous studies to further discuss the possible interference between influenza and COVID-19 in young children.
Ever since the war on cancer was declared in 1971, there has been an explosion in our understanding of this diverse group of diseases. The application of molecular genetics and molecular biology technologies have enabled a deep understanding of the genetic, epigenetic, signaling cascades, survival pathways, and invasive mechanisms that underlie the cancer phenotype. Concomitantly this has translated in the development of ever more effective and safe medications that work through different mechanisms of action and target fundamental aspects of the biology of the tumor. The paradigm has been chronic myeloid leukemia where the discovery of the Philadelphia chromosome, ultimately led to the identification of the BCR-ABL oncogene and the development of tyrosine kinase inhibitors such as imatinib, nilotinib, dasatinib and others and lead to rapid, deep and long-lasting remissions in this disease. Another success story has been acute promyelocytic leukemia with the vast majority of patients now being cured of the disease without the need for any classical chemotherapy.